Increased glutathionylated hemoglobin (HbSSG) in type 2 diabetes subjects with microangiopathy

Objective: Protein glutathionylation is considered an important post-translational modification in the pathogenesis of complex diseases. The aim of this study was to examine whether hemoglobin (Hb) is modified by reduced glutathione (GSH) via oxidation of the thiol groups present in diabetes and its associated microangiopathy and to determine whether oxidative imbalance has any correlation with glutathionylated Hb (HbSSG) levels. Methods: The study group consisted of a total of 130 subjects which included non-diabetic healthy control subjects (n = 30) and type 2 diabetic patients with (n = 53) and without (n = 47) microangiopathy. All subjects were assessed for glycemic and lipidemic status, while diabetic subjects were also assessed for the diagnosis of retinopathy and nephropathy. RBC lysates from all the subjects were analyzed by liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) for HbSSG β-globin chains. Levels of GSH and thiobarbituric acid substances (TBARS) levels were measured by spectrophotometric and fluorimetric methods, respectively. Results: The positivity for HbSSG in diabetic subjects with microangiopathy was significantly higher (69%) compared to diabetics without microangiopathy (22%) and control subjects (14%). In univariate regression analysis, HbSSG levels were significantly associated with the duration of diabetes, HbA1c, and TBARS levels. GSH levels were negatively correlated (r = -0.57, P < 0.001) with HbSSG in diabetic subjects. A significant inverse correlation (r = -0.42, P < 0.001) between the GSH levels and HbA1c levels was also seen in diabetic subjects. Conclusions: This is perhaps the largest LC-MS-based study to demonstrate that HbSSG levels are markedly increased in diabetic subjects with microangiopathy. Since diabetic subjects also exhibited increased lipid peroxidation and decreased GSH levels, it appears that enhanced oxidative stress may account for the increased HbSSG concentrations and altered reduction-oxidation (redox) signaling

Increased glutathionylated hemoglobin (HbSSG) in type 2 diabetes subjects with microangiopathy

Abstract Objective: Protein glutathionylation is considered an important post-translational modification in the pathogenesis of complex diseases. The aim of this study was to examine whether hemoglobin (Hb) is modified by reduced glutathione (GSH) via oxidation of the thiol groups present in diabetes and its associated microangiopathy and to determine whether oxidative imbalance has any correlation with glutathionylated Hb (HbSSG) levels. Methods: The study group consisted of a total of 130 subjects which included non-diabetic healthy control subjects (n = 30) and type 2 diabetic patients with (n = 53) and without (n = 47) microangiopathy. All subjects were assessed for glycemic and lipidemic status, while diabetic subjects were also assessed for the diagnosis of retinopathy and nephropathy. RBC lysates from all the subjects were analyzed by liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) for HbSSG h-globin chains. Levels of GSH and thiobarbituric acid substances (TBARS) levels were measured by spectrophotometric and fluorimetric methods, respectively. Results: The positivity for HbSSG in diabetic subjects with microangiopathy was significantly higher (69%) compared to diabetics without microangiopathy (22%) and control subjects (14%). In univariate regression analysis, HbSSG levels were significantly associated with the duration of diabetes, HbA1c, and TBARS levels. GSH levels were negatively correlated (r = À0.57, P < 0.001) with HbSSG in diabetic subjects. A significant inverse correlation (r = À0.42, P < 0.001) between the GSH levels and HbA1c levels was also seen in diabetic subjects. Conclusions: This is perhaps the largest LC-MS-based study to demonstrate that HbSSG levels are markedly increased in diabetic subjects with microangiopathy. Since diabetic subjects also exhibited increased lipid peroxidation and decreased GSH levels, it appears that enhanced oxidative stress may account for the increased HbSSG concentrations and altered reduction -oxidation (redox) signaling

Effect of integration of supplemental nutrition with public health programmes in pregnancy and early childhood on cardiovascular risk in rural Indian adolescents: long term follow-up of Hyderabad nutrition trial.

OBJECTIVE: To determine whether integration of nutritional supplementation with other public health programmes in early life reduces the risk of cardiovascular disease in undernourished populations. DESIGN: Approximately 15 years' follow-up of participants born within an earlier controlled, community trial of nutritional supplementation integrated with other public health programmes. SETTING: 29 villages (15 intervention, 14 control) near Hyderabad city, south India. PARTICIPANTS: 1165 adolescents aged 13-18 years. INTERVENTION: Balanced protein-calorie supplementation (2.51 MJ, 20 g protein) offered daily to pregnant women and preschool children aged under 6 years, coupled with integrated delivery of vertical public health programmes. MAIN OUTCOME MEASURES: Height, adiposity, blood pressures, lipids, insulin resistance (homoeostasis model assessment (HOMA) score), and arterial stiffness (augmentation index). RESULTS: The participants from the intervention villages were 14 mm (95% confidence interval 4 to 23; P=0.007) taller than controls but had similar body composition. The participants from the intervention villages had more favourable measures of insulin resistance and arterial stiffness: 20% (3% to 39%; P=0.02) lower HOMA score and 3.3% (1% to 5.7%; P=0.008) lower augmentation index. No strong evidence existed for differences in blood pressures and serum lipids. CONCLUSIONS: In this undernourished population, integrated delivery of supplemental nutrition with other public health programmes in pregnancy and early childhood was associated with a more favourable profile of cardiovascular disease risk factors in adolescence. This pragmatic study provides the most robust evidence to date on this important hypothesis for which classic trials are unlikely. Improved maternal and child nutrition may have a role in reducing the burden of cardiovascular disease in low income and middle income countries

Development and validation of resource-driven risk prediction models for incident chronic kidney disease in type 2 diabetes

Prediction models for population-based screening need, for global usage, to be resource-driven, involving predictors that are affordably resourced. Here, we report the development and validation of three resource-driven risk models to identify people with type 2 diabetes (T2DM) at risk of stage 3 CKD defined by a decline in estimated glomerular filtration rate (eGFR) to below 60 mL/min/1.73m2. The observational study cohort used for model development consisted of data from a primary care dataset of 20,510 multi-ethnic individuals with T2DM from London, UK (2007–2018). Discrimination and calibration of the resulting prediction models developed using cox regression were assessed using the c-statistic and calibration slope, respectively. Models were internally validated using tenfold cross-validation and externally validated on 13,346 primary care individuals from Wales, UK. The simplest model was simplified into a risk score to enable implementation in community-based medicine. The derived full model included demographic, laboratory parameters, medication-use, cardiovascular disease history (CVD) and sight threatening retinopathy status (STDR). Two less resource-intense models were developed by excluding CVD and STDR in the second model and HbA1c and HDL in the third model. All three 5-year risk models had good internal discrimination and calibration (optimism adjusted C-statistics were each 0.85 and calibration slopes 0.999–1.002). In Wales, models achieved excellent discrimination(c-statistics ranged 0.82–0.83). Calibration slopes at 5-years suggested models over-predicted risks, however were successfully updated to accommodate reduced incidence of stage 3 CKD in Wales, which improved their alignment with the observed rates in Wales (E/O ratios near to 1). The risk score demonstrated similar model performance compared to direct evaluation of the cox model. These resource-driven risk prediction models may enable universal screening for Stage 3 CKD to enable targeted early optimisation of risk factors for CKD

Increased glutathionylated hemoglobin (HbSSG) in type 2 diabetes subjects with microangiopathy

Objective: Protein glutathionylation is considered an important post-translational modification in the pathogenesis of complex diseases. The aim of this study was to examine whether hemoglobin (Hb)is modified by reduced glutathione (GSH) via oxidation of the thiol groups present in diabetes and its associated micro angiopathy and to determine whether oxidative imbalance has any correlation with glutathionylated Hb (HbSSG) levels. Methods: The study group consisted of a total of 130 subjects which included non-diabetic healthy control subjects (n = 30) and type 2 diabetic patients with (n = 53) and without (n = 47) micro angiopathy.All subjects were assessed for glycemic and lipidemic status, while diabetic subjects were also assessed for the diagnosis of retinopathy and nephropathy. RBC lysates from all the subjects were analyzed by liquid chromatography/electrospray ionization-mass spectrometry(LC/ESI-MS) for HbSSG \beta-globin chains. Levels of GSH and thiobarbituric acid substances (TBARS) levels were measured by spectrophotometric and fluorimetric methods, respectively. Results: The positivity for HbSSG in diabetic subjects with microangiopathy was significantly higher (69%) compared to diabetics without microangiopathy (22%) and control subjects (14%). In univariate regression analysis, HbSSG levels were significantly associated with the duration of diabetes, HbA1c, and TBARS levels. GSH levels were negatively correlated (r = -0.57, P < 0.001) with HbSSG in diabetic subjects. A significant inverse correlation (r = -0.42, P < 0.001)between the GSH levels and HbA1c levels was also seen in diabetic subjects. Conclusions: This is perhaps the largest LC-MS-based study to demonstrate that HbSSG levels are markedly increased in diabetic subjects with microangiopathy. Since diabetic subjects also exhibited increased lipid peroxidation and decreased GSH levels, it appears that enhanced oxidative stress may account for the increased HbSSG concentrations and altered reduction-oxidation (redox) signaling